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Description of key information

The toxicity of melam is low. The NOEL is 1000 mg/kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

The 28-day and the 90-day-toxicity studies did not reveal any local or systemic toxic effect of melam up to to doses of 1000 mg/kg bw. A need for a long-term repeated toxicity study or further toxicity studies can therefore not be derived.

 

Selection of the oral route instead of the dermal route:

The toxicity result and the NOAEL for the oral route are also adopted for the dermal route as it is generally accepted that the dermal NOAEL is higher than the oral one and using the same NOAEL also for the dermal situation is a worst case assumption, see Guidance Document on Information Requirements Chapter R.8.4.2. 

No difference in the toxicity was noted between the acute oral toxicity studies and the acute dermal toxicity study as no toxicity was detected at all in both routes.

It is concluded that no toxicity will be revealed in the dermal repeated dose study too, especially at low exposures as it is expected for humans.

Selection of the oral route instead of the inhalation route:

Melam is not irritant to eyes and skin, and it can be expected therefore that no local but - if any - systemic toxic effects would occur by inhalation. The stability of melam is high, even higher than that of the related substance melamine, and it can be assumed, as with melamine, that no metabolism of melam in the organism and by this no first pass effect occurs. It is therefore expected that the toxic effects after oral and inhalation exposure would be qualitatively the same.

No difference in the toxicity was noted between the acute oral toxicity studies and the acute inhalation toxicity study as no toxicity was detected at all in both routes.

It is concluded that no toxicity will be revealed in the inhalation repeated dose study too, especially at low exposures as it is expected for humans.

The vapour pressure of melam is very low and only insignificant exposures are expected from this source. The exposure of humans will be low, as the conditions during manufacturing will prevent an exposure to dust. Melam is exclusively introduced into plastic material during compounding. It is included by this process into a matrix and is no longer available for inhalation exposure.

 

The following argumentations for a low exposure were taken from the paper "Maximum expected exposure levels in workers and the general population" of T. Tiemersma and Wil ten Berge of DSM Regulatory Affairs & Product Safety Polymers, 6 July 2010, report Tox. 31490a.

"Melam is a solid. For solids exist a general exposure level to prevent irritation of the respiratory tract, that is 10 mg/m3 for inhalable dust and 3 mg/m3 for respirable particles. Commercial melam consists for about 30 % of respirable particles. Respirable particles remain longer airborne and the total concentration will normally be lower than 10 mg/m3, if the respirable particles should not exceed 3 mg/m3 (ACGIH). Respirable particles that are retained in the respiratory tract, will be dissolved in the aqueous mucous layer and mainly absorbed by secondary ingestion.

It is assumed that a worker inhales 10 m3 of air during a working day and that the average bodyweight of the worker is 70 kg. At an average concentration of 10 mg melam per m3 the worker inhales 100 mg/day or 1.43 mg/kg bw/day.

The exposure of consumers should be related to the end use of melam. Melam is used for electronic components in Personal Computers, Televisions, Laptops etc. There is no direct contact by hands touching the components. So the only exposure might be inhalation of vapour, escaping from the electronic components. The highest estimated vapour pressure (an overestimation compared to AC-labs) appears to be 5.2 E-8 Pascal related to pure melam. So an atmosphere saturated with pure melam vapour, contains 5 ng per m3. Due to limited mass transfer (mixed in electronic component material) to the atmosphere, the expected exposure value might be 100 times lower. It is unimaginable, that melam would do any harm to the consumer by inhalation exposure. The inhaled daily dose per day for a consumer is 0.014 nanogram per kg bw/day."

Justification for classification or non-classification

The toxicity of melam is low. The NOEL is 1000 mg/kg bw. No classification is therefore required.